title: Motor pathway injury in patients with periventricular leucomalacia and spastic diplegia.
abstract: Periventricular leucomalacia has long been investigated as a leading cause of motor and cognitive dysfunction in patients with spastic diplegic cerebral palsy. However, patients with periventricular leucomalacia on conventional magnetic resonance imaging do not always have motor dysfunction and preterm children without neurological abnormalities may have periventricular leucomalacia. In addition, it is uncertain whether descending motor tract or overlying cortical injury is related to motor impairment. To investigate the relationship between motor pathway injury and motor impairment, we conducted voxelwise correlation analysis using tract-based spatial statistics of white matter diffusion anisotropy and voxel-based-morphometry of grey matter injury in patients with periventricular leucomalacia and spastic diplegia (n = 43, mean 12.86 ± 4.79 years, median 12 years). We also evaluated motor cortical and thalamocortical connectivity at resting state in 11 patients using functional magnetic resonance imaging. The functional connectivity results of patients with spastic diplegic cerebral palsy were compared with those of age-matched normal controls. Since γ-aminobutyric acid(A) receptors play an important role in the remodelling process, we measured neuronal γ-aminobutyric acid(A) receptor binding potential with dynamic positron emission tomography scans (n = 27) and compared the binding potential map of the patient group with controls (n = 20). In the current study, white matter volume reduction did not show significant correlation with motor dysfunction. Although fractional anisotropy within most of the major white matter tracts were significantly lower than that of age-matched healthy controls (P < 0.05, family wise error corrected), fractional anisotropy mainly within the bilateral corticospinal tracts and posterior body and isthmus of the corpus callosum showed more significant correlation with motor dysfunction (P < 0.03) than thalamocortical pathways (P < 0.05, family-wise error corrected). Cortical volume of the pre- and post-central gyri and the paracentral lobule tended to be negatively correlated with motor function. The motor cortical connectivity was diminished mainly within the bilateral somatosensory cortex, paracentral lobule, cingulate motor area and visual cortex in the patient group. Thalamovisual connectivity was not diminished despite severe optic radiation injury. γ-Aminobutyric acid(A) receptor binding potential was focally increased within the lower extremity homunculus, cingulate cortex, visual cortex and cerebellum in the patient group (P < 0.05, false discovery rate corrected). In conclusion, descending motor tract injury along with overlying cortical volume reduction and reduced functional connectivity appears to be a leading pathophysiological mechanism of motor dysfunction in patients with periventricular leucomalacia. Increased regional γ-aminobutyric acid(A) receptor binding potential appears to result from a compensatory plasticity response after prenatal brain injury.
authors.affiliation: Department of Diagnostic Radiology, Division of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea. jdlee@yuhs.ac
authors.forename: Jong Doo
authors.initials: JD
authors.lastname: Lee
authors.forename: Hae-Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Park
authors.forename: Maeng-Keun
authors.initials: MK
authors.lastname: Oh
authors.forename: Bumhee
authors.initials: B
authors.lastname: Park
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Rha
authors.forename: Sung-Rae
authors.initials: SR
authors.lastname: Cho
authors.forename: Eung Yeop
authors.initials: EY
authors.lastname: Kim
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Park
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Dong Goo
authors.initials: DG
authors.lastname: Kim
authors.forename: Chang Il
authors.initials: CI
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002547:Cerebral Palsy / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D056324:Diffusion Tensor Imaging; D004525:Efferent Pathways / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009929:Organ Size